FGF23signalering

FGF23 signaling refers to the biological pathway mediated by Fibroblast Growth Factor 23 (FGF23), a hormone that plays a crucial role in phosphate and vitamin D metabolism. FGF23 is primarily produced by osteocytes in bone and acts on target cells, notably in the kidneys and parathyroid glands, to regulate these processes.

The FGF23 signaling cascade is initiated when FGF23 binds to a receptor complex on the cell surface. This complex consists of an FGF receptor (FGFR) and a co-receptor, typically one of the klotho proteins (alpha-klotho or beta-klotho). Alpha-klotho is predominantly expressed in the kidneys and parathyroid glands, making them key sites for FGF23 action. Beta-klotho is found in other tissues, suggesting broader roles for FGF23.

Upon binding, FGF23 triggers intracellular downstream signaling events, including the activation of the MAPK/ERK pathway and the PI3K/Akt pathway. These pathways ultimately lead to changes in gene expression that regulate phosphate reabsorption in the kidneys and the production of the active form of vitamin D, calcitriol. Specifically, FGF23 promotes phosphaturia (excretion of phosphate in urine) and suppresses vitamin D activation.

Dysregulation of FGF23 signaling is implicated in various diseases. Conditions like chronic kidney disease are often associated with elevated FGF23 levels, contributing to phosphate imbalance and other metabolic abnormalities. Genetic mutations affecting FGF23, its receptors, or klotho can lead to rare inherited disorders such as autosomal dominant hypophosphatemic rickets. Understanding FGF23 signaling is therefore vital for comprehending and potentially treating these conditions.